DESCRIPTION (Adapted from the Candidate's Abstract) The long term scientific goal of this proposal is to identify and functionally characterize classes of genes that are involved in the mammalian response to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. A gene trap screen in mouse embryonic stem (ES) cells is proposed to do this in a efficient way. This experimental strategy simultaneously identifies novel genes, mutates them, tags them with a reporter molecule, and enables the production of knockout mice carrying the induced mutations. Within the proposed research period, it will be possible to conduct preliminary molecular and functional characterization of the role of these genes in cell cultures and animals. The knockout animals generated by this work will be useful for a variety of future investigations into the effects of environmental agents on mice and humans.